Cytokines are hormone-like molecules that regulate various aspects of an immune or inflammatory response; they exert their effects by specifically binding receptors present on cells, and transducing a signal to the cells. In addition to having beneficial effects (i.e., development of an effective immune response and control of infectious disease), cytokines have also been implicated in various autoimmune and inflammatory conditions.
Various cartilage associated cells (i.e., chondrocytes, synovial lining cells, endothelial cells, synovial fibroblasts and mononuclear cells that are present in a joint) can release nitric oxide (NO). This free radical serves as a front-line antimicrobial agent and also has antitumor effects. However, NO has also been implicated in several deleterious conditions, including autoimmune and inflammatory diseases and the bone destruction that occurs in osteoarthritis, which is not typically thought of as an inflammatory condition.
Rouvier et al. (J. Immunol. 150:5445; 1993) reported a novel cDNA which they termed CTLA-8, and which has since become known as Interleukin-17 (IL-17). IL-17 is 57% homologous to the predicted amino acid sequence of an open reading frame (ORF) present in Herpesvirus saimiri (HSV) referred to as HVS13 (Nicholas et al. Virol. 179:1 89, 1990; Albrecht et al., J. Virol. 66:5047;1992).
A novel receptor that binds IL-17 and its viral homolog, HVS 13, has been, cloned as described in U.S. Ser. No. 08/620,694, filed Mar. 21, 1996 now U.S. Pat. No. 5,869,286. The receptor is a Type I transmembrane protein; the mouse receptor has 864 amino acid residues, the human receptor has 866 amino acid residues. A soluble form of the receptor was found to inhibit various IL-17-mediated activities.